Our efforts will continue to be directed toward elucidating the mechanisms of TSH-receptor interaction and propagation of the biological signal in normal and pathologic thyroid glands. Special emphasis will be placed on elucidating the mechanism by which guanyl nucleotides modulate the coupling of TSH-receptor complexes to adenylate cyclase. We plan to focus our attention on dissecting the adenylate cyclase system by solubilizing and purifying each of the three main components of the system: TSH receptor, guanyl nucleotide binding protein and catalytic unit. By reconstitution of the solubilized components, we hope to establish the stoichiometry of the complex and the molecular events associated with the hormone receptor occupancy of the TSH receptors and, hence, with receptor-effector coupling.